Genetic Variant SF3A2:p.Pro412Thr (chr19-2248385-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007165.5(SF3A2):c.1234C>A(p.Pro412Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SF3A2
NM_007165.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Publications

0 publications found

Variant links:

Genes affected

SF3A2 (HGNC:10766): (splicing factor 3a subunit 2) This gene encodes subunit 2 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 2 interacts with subunit 1 through its amino-terminus while the single zinc finger domain of subunit 2 plays a role in its binding to the 15S U2 snRNP. Subunit 2 may also function independently of its RNA splicing function as a microtubule-binding protein. [provided by RefSeq, Jul 2008]

SF3A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13315266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007165.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A2	NM_007165.5	MANE Select	c.1234C>A	p.Pro412Thr	missense	Exon 9 of 9	NP_009096.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SF3A2	ENST00000221494.10	TSL:1 MANE Select	c.1234C>A	p.Pro412Thr	missense	Exon 9 of 9	ENSP00000221494.3	Q15428
SF3A2	ENST00000866932.1		c.1336C>A	p.Pro446Thr	missense	Exon 9 of 9	ENSP00000536991.1
SF3A2	ENST00000866930.1		c.1234C>A	p.Pro412Thr	missense	Exon 10 of 10	ENSP00000536989.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1229716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

592462

African (AFR)

AF:

0.00

AC:

AN:

24796

American (AMR)

AF:

0.00

AC:

AN:

14102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17456

East Asian (EAS)

AF:

0.00

AC:

AN:

29066

South Asian (SAS)

AF:

0.00

AC:

AN:

52318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1004062

Other (OTH)

AF:

0.00

AC:

AN:

50920

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.048

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.64

M_CAP

Benign

0.073

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PhyloP100

1.9

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.060

REVEL

Benign

0.048

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.029

Polyphen

0.14

Vest4

0.34

MutPred

0.32

Loss of catalytic residue at P411 (P = 0.0116)

MVP

0.29

MPC

0.70

ClinPred

0.45

GERP RS

3.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.15

gMVP

0.22

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over